2-脱氧葡萄糖联合奥希替尼对非小细胞肺癌细胞株H1975耐药性、糖酵解水平表达和增殖活性的影响  

Effects of 2-deoxyglucose combined with osimertinib on drug resistance,glycolysis level expression and proliferation activity of non-small cell lung cancer cell line H1975

作　　者：胡海峰[1] 雒小佳 HU Haifeng;LUO Xiaojia(Second Ward of Department of Oncology,Affiliated Hospital of Yan′an University,Yan′an,Shaanxi 716000,China)

机构地区：[1]延安大学附属医院肿瘤科二病区,陕西延安716000

出　　处：《检验医学与临床》2022年第19期2620-2622,2627,共4页Laboratory Medicine and Clinic

基　　金：陕西省教育厅专项科研计划项目(16JK2031)。

摘　　要：目的探讨2-脱氧葡萄糖联合奥希替尼对非小细胞肺癌细胞株H1975耐药性、糖酵解水平表达和增殖活性的影响。方法将非小细胞肺癌细胞株H1975(美国国家细胞库)经过体外诱导处理后,建立奥希替尼继发性耐药非小细胞肺癌细胞株H1975-OR。观察细胞株H1975-OR与细胞株H1975对奥希替尼的敏感性,奥希替尼对细胞株H1975-OR和细胞株H1975增殖活性的影响,细胞株H1975-OR与细胞株H1975糖酵解水平,2-脱氧葡萄糖是否可逆转细胞株H1975-OR对奥希替尼的耐药性。结果细胞株H1975-OR对奥希替尼的敏感性为(0.95±0.18)μmol/L,低于胞株H1975的(6.99±1.88)μmol/L,差异有统计学意义(P<0.05)。细胞株H1975-OR的糖酵解水平为(20.87±0.86)mmol/L,低于细胞株H1975的(25.93±2.94)mmol/L,差异有统计学意义(P<0.05)。当2-脱氧葡萄糖水平为4 mmol/L时,细胞株H1975-OR对奥希替尼的半抑制浓度(IC50)值为(1.39±0.11)μmol/L,与奥希替尼敏感细胞株H1975的(1.01±0.19)μmol/L相似。奥希替尼对细胞株H1975-OR作用后,细胞存活率如下:G1期,(0.046±0.020)%;G2期,(0.178±0.028)%;G3期,(0.395±0.082)%;G4期,(0.724±0.048)%。结论2-脱氧葡萄糖逆转非小细胞肺癌细胞对奥希替尼的继发性耐药,其机制与抑制细胞糖酵解进而诱导凋亡增加有关。Objective To investigate the effect of 2-deoxyglucose combined with osimertinib on drug resistance,glycolysis level expression and proliferation activity of non-small cell lung cancer(NSCLC)cell line H1975.Methods NSCLC cell line H1975(US National Cell Bank)was induced in vitro to establish secondary osimertinib resistant NSCLC cancer cell line H1975-OR.The sensitivity of cell line H1975-OR and H1975 to osimertinib,the effect of osimertinib on the proliferation activity of cell line H1975-OR and H1975,the glycolysis level of cell line H1975-OR and H1975,and wether the resistance of cell line H1975-OR to osimertinib reversed by 2-deoxyglucose were observed.Results The sensitivity of cell line H1975-OR to osimertinib was(0.95±0.18)μmol/L,which was higher than that of cell line H1975[(6.99±1.88)μmol/L],difference was statistically significant(P<0.05).The glycolysis level of cell line H1975-OR was(20.87±0.86)mmol/L,which was lower than that of cell line H1975[(25.93±2.94)mmol/L](P<0.05).When the level of 2-deoxyglucose was 4 mmol/L,the 50%inhibiting concentration(IC50)value of cell line H1975-OR to osimertinib was(1.39±0.11)μmol/L,which was closed to that of osimertinib sensitive cell line H1975[(1.01±0.19)μmol/L].The viability of osimertinib on cell line H1975-OR was as following:G1,(0.046±0.020)%;G2,(0.178±0.028)%;G3,(0.395±0.082)%;G4,(0.724±0.048)%.Conclusion 2-deoxyglucose can reverse the secondary resistance of NSCLC cells to osimertinib,and its mechanism is related to the inhibition of cell glycolysis and the increase of apoptosis.

关 键 词：2-脱氧葡萄糖 奥希替尼 非小细胞肺癌 耐药性 糖酵解 

分 类 号：R734.2[医药卫生—肿瘤]